Dysregulated methylation at imprinted genes in prostate tumor tissue detected by methylation microarray

Abstract

BackgroundImprinting is an important epigenetic regulator of gene expression that is often disrupted in cancer. While loss of imprinting (LOI) has been reported for two genes in prostate cancer (IGF2 and TFPI2), disease-related changes in methylation across all imprinted gene regions has not been investigated.MethodsUsing an Illumina Infinium Methylation Assay, we analyzed methylation of 396 CpG sites in the promoter regions of 56 genes in a pooled sample of 12 pairs of prostate tumor and adjacent normal tissue. Selected LOI identified from the array was validated using the Sequenom EpiTYPER assay for individual samples and further confirmed by expression data from publicly available datasets.ResultsMethylation significantly increased in 52 sites and significantly decreased in 17 sites across 28 unique genes (P < 0.05), and the strongest evidence for loss of imprinting was demonstrated in tumor suppressor genes DLK1, PLAGL1, SLC22A18, TP73, and WT1. Differential expression of these five genes in prostate tumor versus normal tissue using array data from a publicly available database were consistent with the observed LOI patterns, and WT1 hypermethylation was confirmed using quantitative DNA methylation analysis.ConclusionsTogether, these findings suggest a more widespread dysregulation of genetic imprinting in prostate cancer than previously reported and warrant further investigation.

Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma

“…It has been reported that silencing of miR-126 is induced by promoter methylation of its host gene EGFL7 [11]. Hypermethylation of tumor suppressor genes is frequently observed in cancers [13,14], and such epigenetic changes are potential markers for detecting and monitoring tumors [15][16][17]. Aberrantly methylated cancer-related genes contribute to MM progression and its clinical outcome [18][19][20].…”

WT1 expression is increased in primary fibroblasts derived from Dupuytren’s disease tissues

“…Loss of IGF2 and WT1 imprinting in tumors typically results in up regulated expression levels (Brown et al 2008;Jacobs et al 2013), and our recent unpublished findings suggest that IGF2 imprinting may be lost in a subset of patients with DD. As both IGF2 and WT1 expression levels are up regulated in DD cells, we will include WT1 in these ongoing studies to determine if abnormal epigenetic regulation of expression contributes to the increased IGF2 and WT1 transcript levels in this fibrosis.…”

Differentially methylated CpG sites associated with the high-risk group of prostate cancer

“…Presently, there are no data on the methylation status of ARHGEF4, MYOF, WT1, PTAFR, SCYL3, and VPS13D in the literature ( Table 4 ). Nevertheless, ARHGEF4 [ 52 ], [ 53 ] , MYOF [ 54 ], [ 55 ], [ 56 ] , WT1 [ 57 ], [ 58 ] , PTAFR [ 59 ] were upregulated in pancreatic, breast, and prostate cancers.…”